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This chapter reviews the current status of γ-secretase modulators, highlighting key compounds by each company involved in the area. The review focuses on the three main chemotypes: acids, imidazoles and related derivatives and natural products. A section on chemical biology and ligand-binding site elucidation studies is also included. The primary source of information is drawn from peer reviewed literature as this permits analysis of PK-PD relationships and subsequent comment. Discussion of the patent literature is included for completeness. From this analysis, the key issues and challenges in the area are highlighted. The review concludes with a summary of the clinical development status and comment on future prospects of the field.
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http://dx.doi.org/10.1016/B978-0-444-63380-4.00003-2 | DOI Listing |
Crit Rev Immunol
January 2025
Department of Pharmacy, Birla Institute of Technology and Science (BITS) Pilani, Hyderabad Campus, Dist. Medchal,500078, Telangana State, India.
Caseinolytic protease P (ClpP) is a highly conserved serine protease that plays a pivotal role in protein homeostasis and quality control in bacteria, mitochondria of mammalian cells, and plant chloroplasts. As the proteolytic core of the ATP-dependent Clp protease complex, ClpP partners with regulatory ATPases (e.g.
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January 2025
Department of Biochemistry, University of Kerala, Kariavattom, Thiruvananthapuram, Kerala, India 695581.
Rheumatoid arthritis (RA) is a chronic autoimmune condition that impacts the immune system, especially through changes in the splenic immune cell system. This review provides an overview of the role of splenocytes in T cell signaling and their immune response in RA patients. The spleen acts as a critical site for the activation and differentiation of splenic immune cells like T cells, B cells, macrophages, dendritic cells, and NK cells.
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January 2025
Department of Pharmacy, Birla Institute of Technology and Science (BITS) Pilani, Hyderabad Campus, Dist. Medchal,500078, Telangana State, India.
IL-2 agonists significantly modulate T cell regulation, impacting activation, proliferation, differentiation, and immune homeostasis. Interleukin-2 (IL-2) is crucial for T cell growth and function, binding to the IL-2 receptor to trigger signaling pathways that balance immune responses. IL-2 promotes the expansion of effector T cells and enhances regulatory T cells (Tregs), preventing autoimmune responses.
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January 2025
Department of General Surgery, The Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300150, China.
Objective: This study aimed to probe the role of Shenling Baizhu powder (SLBZP) in inhibiting breast cancer (BC) lung metastasis, focusing on epithelial-to-mesenchymal transition (EMT) and ferroptosis.
Methods: BC 4T1 cells were treated with low (3.13 µg/mL) and high (12.
Crit Rev Immunol
January 2025
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, China.
Stemming from human immune organs, tonsil-derived mesenchymal stem cells (TMSCs) hold unique strengths in differentiation potential and immune regulatory functions. These characteristics make them valuable for therapeutic applications, particularly in regenerative medicine and autoimmune disease treatment, as they can modulate immune responses and promote tissue repair. Their ability to interact with various cell types and secrete a range of bioactive molecules further enhances their role in orchestrating healing processes, making them a promising avenue for innovative therapies aimed at restoring balance in the immune system and facilitating recovery from injury or disease.
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